Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy:A Randomised, Double-blind, Multicentre, Phase 3b Study (BESIDE)

摘要

Background: Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic mono therapy.Objective: To evaluate efficacy, safety/tolerability of combination (solifenacin5 mg/mirabegron 50 mg) vs solifenacin 5 or 10 mg in OAB patients remaining incontinent after 4-wk solifenacin 5 mg.Design, Setting, and Participants: OAB patients remaining incontinent despitedaily solifenacin 5 mg during 4-wk single-blind run-in, were randomised 1:1:1 to double-blind daily combination, solifenacin 5 or 10 mg for 12 wk. Patients receiving combination were initiated on mirabegron 25 mg increasing to 50 mg after week 4.Outcome Measurements and Statistical Analysis: Primary endpoint: change from baseline to end of treatment (EOT) in mean number of incontinence episodes/24 (stratified rank ANCOVA). Key secondary endpoints: change from baseline to EOT in mean number of micturitions/24 h (ANCOVA) and number of incontinence episodes during 3-d diary at EOT (mixed effects Poisson regression). BESIDE tested the superiority of combination vs solifenacin 5 mg, noninferiority (and potential superiority) of combination vs solifenacin 10 mg (key secondary endpoints), and safety/tolerability of combination vs Solifenacin monotherapy.Results and Limitations: 2174 patients were randomised: combination (n=727), solifenacin 5mg (n=728) or 10 mg (n=719). At EOT, combination was superior to solifenacin 5 mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p0.001) and incontinence during 3-d diary (p=0.014). Combination was noninferior to BESIDE Primary Final resubmission draft January 2016 4 solifenacin 10 mg for key secondary endpoints, and superior vs solifenacin 10 mg for improving daily micturitions. All treatments were well tolerated.Conclusions: Adding mirabegron 50 mg to solifenacin 5 mg further improved OAB symptoms vs solifenacin 5 or 10 mg, and was well tolerated in OAB patients remaining incontinent after initial solifenacin 5 mg